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In Spain, the largest human West Nile virus (WNV) outbreak among humans was reported in 2020, constituting the second most important outbreak in Europe that season. Extremadura (southwestern Spain) was one of the affected areas, reporting six human cases. The first autochthonous human case in Spain was reported in Extremadura in 2004, and no other human cases were reported until 2020. In this work, we describe the first WNV human outbreak registered in Extremadura, focusing on the most important clinical aspects, diagnostic results, and control actions which followed. In 2020, from September to October, human WNV infections were diagnosed using a combination of molecular and serological methods (an in-house specific qRT-PCR and a commercial ELISA for anti-WNV IgM and IgG antibodies) and by analysing serum, urine, and/or cerebrospinal fluid samples. Serological positive serum samples were further tested using commercial kits against related flaviviruses Usutu and Tick-borne encephalitis in order to analyse serological reactivity and to confirm the results by neutralisation assays. In total, six cases of WNV infection (five with neuroinvasive disease and one with fever) were identified. Clinical presentation and laboratory findings are described. No viral RNA was detected in any of the analysed samples, but serological cross-reactivity was detected against the other tested flaviviruses. Molecular and serological methods for WNV detection in various samples as well as differential diagnosis are recommended. The largest number of human cases of WNV infection ever registered in Extremadura, Spain, occurred in 2020 in areas where circulation of WNV and other flaviviruses has been previously reported in humans and animals. Therefore, it is necessary to enhance surveillance not only for the early detection and implementation of response measures for WNV but also for other emerging flaviviruses that could be endemic in this area.

Resumen: Objetivo: Estudiar la evolución del perfil clínico de una población dada de alta con diagnóstico principal de insuficiencia cardíaca (IC) en las dos primeras décadas del siglo y las variables predictoras de mortalidad y reingreso en el primer año de alta. Diseño: Estudio observacional, retrospectivo, longitudinal. Emplazamiento: Área de salud Don Benito-Villanueva de la Serena, Badajoz, España. Participantes: Todos los pacientes dados de alta con diagnóstico principal de IC entre 2000 y 2019 en un complejo hospitalario general. Mediciones principales: Se recogieron variables sociodemográficas y clínicas, y se realizó un seguimiento de un año; la variable resultado fue un compuesto de mortalidad y/o reingreso. Resultados: Se incluyeron 4.107 altas, edad media 77,1 (DE 10,5) años, 53,1% de mujeres. El número de ingresos, la edad, los antecedentes de neoplasias, los ictus, la insuficiencia renal y la anemia fueron en aumento, así como los reingresos (p de tendencias

Abstract Background An Advanced Care Planning (ACP) program of health decisions is the result of a process of reflection and relationship-building between the patient, their relatives and health professionals. It is based on respect for patients’ autonomy, involving them in making decisions about their disease in a way that is shared between the medical team, the patient and their relatives. Up until now, the efficacy of an ACP has not been measured in the existing literature, and therefore it is unknown if these programs reach their goal. The main objective of our study is to evaluate the efficacy of an ACP program for decision-making in patients with advanced heart failure (HF) in comparison to usual follow up and care. This objective will be evaluated by the Patient Activation Measure test, which measures the participation and self-management of the patient in decision-making. Secondary objectives: to evaluate the effect of the program on quality of life, to know if the patients wishes expressed through the ACP program are fulfilled, to measure the impact of the program on patients’ caregivers, to determine the satisfaction of patients included in the program and to evaluate the effect on quality of death. Methods Randomized multicentre clinical trial at four hospitals in Madrid. Once they are included in the study, patients’ allocation to groups (control vs intervention) will be made by alternative sampling. ACP will be applied to the intervention group, whereas in the Control Group usual follow-up will be carried out in HF units. All patients will fulfil questionnaires and tests related to the objectives of the study again after a 12-month follow-up period in order to gauge the effect of ACP in patients with advanced HF. Discussion The characteristics of patients with advanced HF make them a model for designing ACP programs, given the high prevalence of this disease, the progressive increase in its incidence and it’s clinical characteristics. Until now, the efficacy of this type of program has not been measured, so this Clinical Trial can provide relevant data for future ACP projects. Trial registration ClinicalTrials.gov Identifier: NCT04424680. Registered 9 June 2020. Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT04424680?term=NCT04424680&draw=2&rank=1 .

Long-COVID is a new emerging syndrome worldwide that is characterized by the persistence of unresolved signs and symptoms of COVID-19 more than 4 weeks after the infection and even after more than 12 weeks. The underlying mechanisms for Long-COVID are still undefined, but a sustained inflammatory response caused by the persistence of SARS-CoV-2 in organ and tissue sanctuaries or resemblance with an autoimmune disease are within the most considered hypotheses. In this study, we analyzed the usefulness of several demographic, clinical, and immunological parameters as diagnostic biomarkers of Long-COVID in one cohort of Spanish individuals who presented signs and symptoms of this syndrome after 49 weeks post-infection, in comparison with individuals who recovered completely in the first 12 weeks after the infection. We determined that individuals with Long-COVID showed significantly increased levels of functional memory cells with high antiviral cytotoxic activity such as CD8+ TEMRA cells, CD8±TCRγδ+ cells, and NK cells with CD56+CD57+NKG2C+ phenotype. The persistence of these long-lasting cytotoxic populations was supported by enhanced levels of CD4+ Tregs and the expression of the exhaustion marker PD-1 on the surface of CD3+ T lymphocytes. With the use of these immune parameters and significant clinical features such as lethargy, pleuritic chest pain, and dermatological injuries, as well as demographic factors such as female gender and O+ blood type, a Random Forest algorithm predicted the assignment of the participants in the Long-COVID group with 100% accuracy. The definition of the most accurate diagnostic biomarkers could be helpful to detect the development of Long-COVID and to improve the clinical management of these patients.

The clinical presentations of COVID-19 may range from an asymptomatic or mild infection to a critical or fatal disease. Several host factors such as elderly age, male gender, and previous comorbidities seem to be involved in the most severe outcomes, but also an impaired immune response that causes a hyperinflammatory state but is unable to clear the infection. In order to get further understanding about this impaired immune response, we aimed to determine the association of specific HLA alleles with different clinical presentations of COVID-19. Therefore, we analyzed HLA Class I and II, as well as KIR gene sequences, in 72 individuals with Spanish Mediterranean Caucasian ethnicity who presented mild, severe, or critical COVID-19, according to their clinical characteristics and management. This cohort was recruited in Madrid (Spain) during the first and second pandemic waves between April and October 2020. There were no significant differences in HLA-A or HLA-B alleles among groups. However, despite the small sample size, we found that HLA-C alleles from group C1 HLA-C*08:02, -C*12:03, or -C*16:01 were more frequently associated in individuals with mild COVID-19 (43.8%) than in individuals with severe (8.3%; p = 0.0030; pc = 0.033) and critical (16.1%; p = 0.0014; pc = 0.0154) disease. C1 alleles are supposed to be highly efficient to present peptides to T cells, and HLA-C*12:03 may present a high number of verified epitopes from abundant SARS-CoV-2 proteins M, N, and S, thereby being allegedly able to trigger an efficient antiviral response. On the contrary, C2 alleles are usually poorly expressed on the cell surface due to low association with β2-microglobulin (β2M) and peptides, which may impede the adequate formation of stable HLA-C/β2M/peptide heterotrimers. Consequently, this pilot study described significant differences in the presence of specific HLA-C1 alleles in individuals with different clinical presentations of COVID-19, thereby suggesting that HLA haplotyping could be valuable to get further understanding in the underlying mechanisms of the impaired immune response during critical COVID-19.

Chromodomain-helicase-DNA-binding protein 4 (CHD4) is an epigenetic regulator identified as an oncogenic element that may provide a novel therapeutic target for the treatment of breast cancer (BC). CHD4—the core component of the nucleosome remodeling and deacetylase (NuRD) complex—may be mutated in patients with this disease. However, information on CHD4 mutants that might allow their use as biomarkers of therapeutic success and prognosis is lacking. The present work examines mutations in CHD4 reported in patients with breast cancer and included in public databases and attempts to identify their roles in its development. The databases revealed 81 point mutations across different types of breast cancer (19 of which also appeared in endometrial, intestinal, nervous system, kidney, and lymphoid organ cancers). 71.6% of the detected mutations were missense mutations, 13.6% were silent, and 6.2% nonsense. Over 50% affected conserved residues of the ATPase motor (ATPase and helicase domains), and domains of unknown function in the C-terminal region. Thirty one mutations were classified in the databases as either ‘deleterious’, ‘probably/possibly damaging’ or as ‘high/medium pathogenic’; another five nonsense and one splice-site variant were predicted to produce potentially harmful truncated proteins. Eight of the 81 mutations were categorized as putative driver mutations and have been found in other cancer types. Some mutations seem to influence ATPase and DNA translocation activities (R1162W), while others may alter protein stability (R877Q/H, R975H) or disrupt DNA binding and protein activity (R572*, X34_splice) suggesting CHD4 function may be affected. In vivo tumorigenecity studies in endometrial cancer have revealed R975H and R1162W as mutations that lead to CHD4 loss-of-function. Our study provides insight into the molecular mechanism whereby CHD4, and some of its mutants could play a role in breast cancer and suggest important implications for the biological comprehension and prognosis of breast cancer, identifying CHD4 as a novel therapeutic target for BC patients.

ABSTRACT Background: the use of proton pump inhibitors (PPI) has increased substantially during the last years, possibly due to a significant proportion of prescriptions that do not follow the approved indications. Objective: to assess the prevalence of PPI prescription and the appropriateness of the prescription within the Emergency Department (ED) of a Spanish university hospital. Materials and methods: a cross-sectional, retrospective prescription-indication drug-use study was performed, which selected 384 patients that presented to the ED over two days in January 2016. Results: of the total cohort, 23.2% were taking PPI before their hospital visit and only 20.2% had a correct indication and dosage; 2.9% of the patient cohort had an indication for PPI treatment but had not been prescribed them. A drug other than omeprazole was used in 25% of cases; 30.47% of the patients were discharged with a PPI and only 28.2% of them had the correct indication and dosage. Finally, 5.7% were not prescribed PPI even though it was warranted. PPI prescription increased with age whereas the indication for the prescription decreased. Furthermore, the use of these drugs was higher in hospitalized patients compared to discharged patients. Conclusions: these results are in line with similar studies, which demonstrate the existence of an over-prescription of PPI. PPI prescription needs to be improved, thereby reducing drug interactions, adverse effects and unnecessary economical expenses.

La fresa es una de las frutas más importantes en el mundo, por sus múltiples usos industriales, medicinales y culinarios . En Colombia, la producción se concentra en los departamentos de Cundinamarca, Antioquia, Norte de Santander, Cauca y Boyacá . Su crecimiento y productividad están determinados por una adecuada fertilización en elementos, como nitrógeno (N), potasio (K), calcio (Ca) y fósforo (P), siendo el P un elemento de gran importancia, en diversos procesos fisiológicos, pero con baja disponibilidad para las plantas, en suelos con condiciones de acidez . Por esta razón, el objetivo de la investigación fue evaluar el efecto de una fuente no convencional de fósforo (termofosfato), en el crecimiento y en la producción de plantas de fresa cv . ‘Albión’, bajo condiciones del municipio de Viracachá, Boyacá. Se utilizó un diseño experimental completamente al azar, con 4 tratamientos, que correspondieron a dosis crecientes de ter- mofosfato (0, 300, 600 y 900kg ha-1), con 4 repeticiones . Se evaluó el contenido de clorofilas totales, peso seco de parte aérea y raíz, número de estructuras reproductivas, producción de frutos, concentración foliar de P, Ca y silicio (Si) . Se presentaron diferencias significativas (P≤0,05) en las varia- bles clorofilas totales, peso seco de raíz, producción por calidad, concentración foliar de P y Si; las demás variables no mostraron diferencias estadísticas. Los mejores resultados, se presentaron con los tratamientos de 300 y 600kg ha-1 de termofosfato, convirtiéndolo en una alternativa de suministro en suelos con problemas de acidez y baja disponibilidad de P .

Enfrentados a una crisis del orden social y político, y considerando insuficiente la represión estatal y paraestatal desarrollada por los gobiernos peronistas, sectores dominantes y dirigentes optaron por construir un Estado Terrorista. A partir de 1976, la acción estatal en su conjunto diseminó un terror sistemático más allá de los centros clandestinos de detención, procurando un disciplinamiento social absoluto. Ante ello, la construcción de colectivos sociales (como los nuevos organismos de derechos humanos surgidos de las luchas de los familiares de detenidosdesaparecidos) constituyeron acciones de resistencia. En base a una pluralidad de fuentes, recuperaremos aquí algunos aspectos de la conformación de Madres de Plaza de Mayo: su especificidad, las dificultades de crear “Madres” en el apogeo de la violencia estatal, sus primeras interpelaciones a la faz pública del Estado Terrorista, entre otros. A partir de fuentes orales, nuestra investigación procura indagar especialmente sobre los sentidos dados a sus luchas ante el terrorismo estatal. Desde la Historia Oral, analizamos significados construidos por las propias Madres sobre sus orígenes y el conjunto de sus experiencias políticas durante la última dictadura (1976-1983). En sus relatos, exploramos sus evocaciones y necesarios “olvidos”, sus representaciones. En sus narraciones conversacionales -como categorizara R. Grele a las entrevistas- surgieron diversos relatos personales: en algunos casos legitiman algunas concepciones dominantes; en otros las cuestionan y avanzan hacia la elaboración de significados alternativos. En muchos casos resultaron/resultan nuevas formas de resistencia.